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Treating Patients After Manic Episodes: Continued Neuroleptic Medication May Be Detrimental

Relapse, study discontinuation, and depressive symptoms were some of the adverse outcomes associated with continued perphenazine use in patients with remitted mania.

Researchers have estimated that that more than two thirds (in one study, as many as 95%) of patients with bipolar disorder continue receiving typical neuroleptics for lengthy periods following remission of manic or mixed episodes. To learn more about the effects of this treatment, these investigators conducted a study involving 37 patients with bipolar disorder (average length of illness, approximately 11 years) and manic episodes who responded to open treatment with mood stabilizers (lithium, divalproate, carbamazepine, or a combination of these drugs) and the neuroleptic perphenazine. After mania remitted, patients continued taking their mood stabilizers, entered the double-blind study, and were randomized to either perphenazine (average dosage, 28.2 mg/day) or placebo for 6 months.

More perphenazine recipients than placebo recipients relapsed to depression during the 6 months (4/19 vs. 0/18), discontinued the study (10/19 vs. 3/18), and experienced dysphoria, depressive symptoms, and extrapyramidal symptoms.

Comment: Rather than benefiting patients, continuation of perphenazine treatment at this average dosage was associated with worse outcomes. These results should give pause to clinicians who routinely continue antipsychotic medications following remission from manic episodes. We need studies to examine the impact of other antipsychotic agents (including atypical antipsychotics) and to ascertain whether these findings are specific to typical neuroleptics, are related to dose, or are more widely generalizable.

— Joel Yager, MD

Published in Journal Watch Psychiatry January 29, 2004

Citation(s):

Zarate CA Jr. and Tohen M. Double-blind comparison of the continued use of antipsychotic treatment versus its discontinuation in remitted manic patients. Am J Psychiatry 2004 Jan; 161:169-71.

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